The goal of this research is to examine the effect of coordination geometry and ligation of the interaction of Cu (II) complexes with DNA, and to determine its relationship to cytotoxic activity. A series of Cu (II) complexes of varied geometries designed to promote binding site specificity will be synthesized and their interaction with DNA assessed. The degree of intercalation, covalent and phosphate binding to DNA will be evaluated using Thermal Denaturation curves, Topisomerization, gel- electrophoresis, viscometry and U.V.-visible spectroscopy to determine the binding constants. Coordination effects on DNA cleavage reactions induced by U.V. radiation and chemical reductants will also be studied using gel electrophoresis. An attempt will be made to correlate these results with observed cytotoxicity and anti-tumor activity.